The present invention relates generally to a method for operating a system for separating constituents of blood and particularly relates to a method of wetting the plasmapheresis filter of a plasma/cell concentrate separation device with anticoagulant.
There are a number of automated, on-line donor, plasmapheresis systems for the separation of whole blood into two or more of its constituents including, for example, plasma and blood cell concentrate. Such systems are designed to collect a predetermined volume of plasma from a donor using a fully automated processing program in conjunction with a plasmapheresis instrument and a disposable tubing set or harness packaged separately from the instrument. One such system is the Autopheresis-C Plasmapheresis System manufactured by Baxter Healthcare Corporation, a wholly-owned subsidiary of the assignee of the present invention.
In that system, a microprocessor controls a number of pumps, clamps, detectors, monitoring systems, etc., for automating the collection of whole blood from the donor, separating the blood into plasma and cell concentrate, collecting the plasma and reinfusing the cell concentrate to the donor using a disposable tubing set or harness installed in the instrument. Generally, the tubing set includes a venous phlebotomy needle for whole blood collection and blood concentrate reinfusion, a separator for separating anticoagulated whole blood into plasma and cell concentrate, a plasma collection container for receiving the plasma from the separator, a reinfusion reservoir from which cell concentrate flows back to the donor during reinfusion and a length of tubing runs for connection with other parts of the instrument and its various pumps, clamps and detectors. Thus, upon installation of the tubing set in the instrument and various setup procedures, the instrument operates to alternate between collection and reinfusion cycles. In the collection cycle, anticoagulated whole blood is pumped by a blood pump to the separator of the tubing set where it is separated into plasma which flows to a collection container and cell concentrate which flows to the reinfusion reservoir. In the reinfusion cycle, the blood pump reverses to flow cell concentrate from the reservoir through the phlebotomy needle to the donor.
More particularly, in the above-described system, a hydrophilic filter is used to effect the separation of the plasma and cell concentrate in the separation device. In using such separation device, it has been found necessary to wet its filter before it comes into contact with the whole blood. The degree of this effect depends greatly on the composition of the filter. For instance, nylon requires prior wetting; polycarbonate does not. If the nylon filter is not first wetted before blood contact, the first plasma that penetrates the filter can contain an undesirably high concentration of hemoglobin. Without wetting, the transfilter pressure required to displace this first plasma portion across the filter is also quite high and much higher than if the filter is already been wetted. It is also believed that this initial high transfilter pressure contributes to a certain degree of plugging of the filter which results in lower plasma flows and which plugging and lower plasma flows do not occur if the filter is initially wetted. Because saline solution was used in the system for other purposes, such system has, in the past, been modified to initially wet the filter with saline. This is accomplished during initial setup of the tubing and prior to any blood collection from the donor. By wetting the separation filter with saline, hemolysis of the first plasma portion through the filter is avoided. Additionally, the large buildup of transfilter pressure and the subsequent more rapid plugging of the filter are similarly avoided.
Recently, however, interest has been demonstrated in plasmapheresis with protocols that do not require saline. Consequently, it is intended to modify a conventional plasmapheresis system to eliminate the mechanisms and procedures for the introduction of saline into the tubing harness except with respect to the emergency administration of saline if required. However, the requirement to wet the filter to avoid hemolysis of the first plasma portion, as well as to retain the other advantages of wetting mentioned above, remain.
Because the only aqueous solution left in the system is anticoagulant, it was initially believed that anticoagulant could be used to wet the filter through the previously used saline line. That is, two asceptic spike penetrations into the anticoagulant bag would be provided, one with the normal anticoagulant spike and the other with the existing saline spike. There is danger, however, in that it is possible for the existing saline spike line to come out of its clamp and thus have anticoagulant administered in an uncontrolled manner to the donor. This is dangerous because anticoagulant generally is composed of citrate which chemically binds to calcium in the donor's body. Too much citrate binds too much calcium, which can cause physiological effects in the donor from mild paraesthesia to cardiac arrest, depending on the quantities involved.
Another proposed solution was to wet the filter of the separation device with anticoagulant through the anticoagulant line in the blood tubing and directly onwards to the separation device in a manner similar to that used in the part with saline solutions. It was found, however, that a substantial quantity about (e.g., 25 ml) of anticoagulant was necessary in order to initially reach the separation device and thereby to initially wet the filter. Because that initial quantity of anticoagulant would have to be returned to the donor at the end of the first collection cycle, there was the undesirable potential for citrate reactions by the donor. Consequently, there was the need for a method of wetting the filter of the separation device in a manner which would avoid hemolysis of the plasma, initial build-up of transfilter pressure and later plugging of the filter, yet which would have no adverse effects on the donor and would minimally impact the current system setup.
Now, however, we have discovered a way to successfully use available anticoagulant for pre-wetting the filter while yet avoiding all the above-mentioned possible disadvantages. Only a limited volume of anticoagulant is passed into a blood supply conduit in advance of the blood. Thus, as the blood later initially passes through the conduit, it pushes ahead of it the limited volume anticoagulant charge thereby to pre-wet the filter as it initially passes into the downstream separation device.
According to the present invention, there is provided a method for wetting the filter of the separation device with anticoagulant. To accomplish this, the tubing harness is applied to the instrument as before. However, only a small amount (e.g., about 6-7 ml) of anticoagulant is first primed into the system. Thus, the blood line clamp is closed, the reinfusion line clamp is open and the anticoagulant pump and blood pump are operated to supply anticoagulant from the anticoagulant supply past its Y-connection with the blood line sufficiently such that there is only a small charge of anticoagulant in the blood line in advance of any whole blood entering the system after venepuncture. This anticoagulant prime continues until a predetermined quantity or charge of anticoagulant is supplied to the blood line and detected in the blood line, preferably by the system air detector. The air detector then signals the microprocessor to stop the anticoagulant prime in the blood line, preferably such that the blood line may contain a small additional quantity of anticoagulant beyond the air detector. Once stopped, various conventional procedures are performed by the instrument in setting up for blood collection and reinfusion with respect to a particular donor.
After such setup and following venepuncture performed on the donor, the blood line clamp between the plasma separation device and the blood pump is opened and the reinfusion line clamp between the reinfusion reservoir and the blood line is closed. This initially supplied limited charge of anticoagulant is then pumped by the blood pump through the blood line so as to advance (prior to the incoming blood supply) into the separation device so as to pre-wet the filter. It will be appreciated that anticoagulated whole blood follows behind this leading charge of anticoagulant in the blood line and forms a whole blood/anticoagulant charge interface. Sufficient blood is pumped such that the initial charge of anticoagulant reaches and wets the filter. This may be detected by, for example, counting a predetermined number of turns of the blood pump and providing a signal in response thereto. The tubing runs are such that the signal indicates that sufficient anticoagulated whole blood has been pumped to enable the initial anticoagulant charge to reach the separation device and wet the filter (before any blood reaches the filter). That detection signal enables the instrument to proceed to the next step, e.g., to prime the reinfusion reservoir with whole blood. Thus, after the filter of the separation device is wetted, the blood line clamp is closed and the reinfusion line clamp is opened and the blood line pump is operated to flow anticoagulated whole blood into the bottom of the reinfusion reservoir. Once this priming is complete, the reinfusion line clamp is closed and the blood line clamp is opened, thereby initiating the first collection cycle. By using this sequence of operation, the fluid first flowing into the separation device constitutes the initial anticoagulant filter wetting charge, followed immediately by anticoagulated whole blood.
According to a preferred embodiment of the present invention, there is provided a method of wetting a plasmapheresis filter with anticoagulant in a plasmapheresis system having a venepuncture needle and a plasma separation device connected by a fluid conduit comprising the steps of providing the conduit with a predetermined amount of anticoagulant, performing the venepuncture to provide the conduit with whole blood from a donor, and pumping the whole blood in the conduit such that a limited volume of anticoagulant in the conduit is provided to the separation device first and in advance of whole blood to wet the plasmapheresis filter before substantial contact with whole blood. Preferably, only a small predetermined amount of anticoagulant is received in the reservoir, for example, on the order of 3 to 4 ml, and preferably no more than about 5 ml as a result of initially wetting the filter with anticoagulant in accordance with this invention. This small amount of anticoagulant returned to the donor at the end of the first cycle has no clinical physiological significance.
Accordingly, it is a primary object of the present invention to provide a novel and improved method for wetting the plasmapheresis filter of a blood separation device with anticoagulant in a manner to achieve the beneficial purposes of initially wetting the filter, i.e., avoiding hemolysis of initial plasma portions, large buildup in transfilter pressure and later plugging of the filter, and without adverse effect on the donor when this wetting charge of anticoagulant is subsequently infused back into the donor.
These and further objects and advantages of the present invention will become more apparent upon reference to the following specification, appended drawings and claims.